P_.ROVIDED. Pdncipal Investigator/Program Director (Last, first, middle): Tomlinson, Andrew A critical question in retinal development is how different photoreceptor types are specified and positioned within a retina. The Drosophila eye is a valuable model system with which to address this question. The fly eye is a compound aggregate of many hundred sub-units called ommatidia. Within each ommatidium there are distinct photoreceptor types and ommatidia occur as different classes containing varying photoreceptor types. The photoreceptor types differ by their opsin expressions, their axonal projections, and their positions within the ommatidia. The major questions we are addressing here are: (i) how the photoreceptors within each ommatidium are uniquely specified? (ii) How the different types of ommatidia are specified? (I) Specification of the R7photoreceptor: The UV sensitive photoreceptor in each ommatidium is the R7 cell. Signals from differentiating photoreceptors that contact the presumptive R7 and activate two distinct intra- cellular signals within the cell - the Ras and Notch (N) pathways. We wish to understand how these two pathways interact to specify the R7 cell. Do they act combinatorially to provide the R7 precursor with a unique developmental cue, or do they act in a different manner? For example could N pathway activation allow the activation of the Ras pathway and have no other function? Once these questions are answered we will examine the nature of the molecular interaction, and or integration of the two pathways. (2) Specification of asymmetry within the ommatidia: The photoreceptors in each ommatidium are arrayed in an asymmetric manner that is critically related to the optical properties of the eye. Ommatidia decode graded information the retina to establish an initial asymmetry that is then communicated to the other cells of the ommatidium. The questions here are how the graded information is established, and how it is decoded and communicated to all cells of the unit. (3) The specification of the dorsal rim: The dorsal rim ommatidia are polarized light detectors cells found in the dorsal extreme of the eye and contain specializations of the R7 and R8 ceils. Signals emanating from the neighboring head tissue induce these ommatidia in only dorsal tissues. W e wish to understand how signals from the head tissue organize the dorsal rim ommatidia and other associated retinal specializations.